The invention relates to a method for forming an emulsion in a fluidic microsystem, wherein a continuous and at least one dispersed phase of the emulsion are produced from at least two different liquids in a dispersion region of the microsystem. The invention also relates to a fluidic microsystem which has at least one dispersion region for forming the emulsion. The invention also relates to a method for processing an emulsion in a fluidic microsystem, wherein droplets of a dispersed phase are fused under the effect of an electric field. The invention also relates to a fusion device for fusing dispersed droplets by means of electrocoalescence.
It is generally known to use fluidic microsystem technology in particular for chemical, biochemical, pharmaceutical or medical analyses. A fluidic microsystem contains channels or cavities having typical cross-sectional dimensions in the sub-mm range, through which liquids can flow. In the microsystem, the liquids or particles suspended therein can undergo physical or chemical treatments or measurements. One particular property of fluidic microsystems is that, due to the small cross-sectional dimensions, the flows are typically laminar and free of eddies, so that targeted control of the flows is possible. One significant advantage, particularly for chemical applications (“lab-on-a-chip”), is provided by the low substance consumption when using the microsystem technique.
A new branch of fluidic microsystem technology that has been developed is known as digital microfluidics, in which a liquid in the microsystem consists not of individual phases but rather of a plurality of phases (compartments) which are delimited from one another. The compartmentalized liquid forms a dispersion (emulsion) consisting of two or more liquids which do not mix within the microsystem. The use of compartmentalized liquids has the particular advantage that the substance consumption can be further reduced since e.g. one specific reaction partner is contained in only a few droplets of a dispersed phase of the emulsion. A further advantage consists in the complete prevention of axial dispersion in the compartmentalized liquid (see e.g. H. Song et al. in “Angew. Chem.”, vol. 792, 2003, page 1145).
Various techniques for forming emulsions in fluidic microsystems are known, which differ by the mechanism for producing and distributing droplets of the dispersed phase in a continuous phase. In the so-called jet technique (see e.g. Y-C. Tan et al. in “LabChip”, vol. 4, 2004, pages 292-298), an initially single-phase liquid, which after formation of the emulsion is to form the dispersed phase, flows at a high speed into a surrounding fluid which is to form the continuous phase after formation of the emulsion. During this, a liquid jet which is delimited from the surroundings is produced, which as a result of the so-called Rayleigh instability breaks down into individual droplets after a predefined jet length. Disadvantages of the jet technique are that it cannot readily be implemented in the microsystem during continuous operation (“on-line”), but rather requires the production of the emulsion outside the microsystem (“off-line”). There are also disadvantages since the rapidly flowing liquid jet results in a high substance consumption and low controllability of the emulsion formation. In the shear technique (see T. Thorsen et al. in “Phys. Review Letters”, vol. 86, 2001, pages 4163-4166), the emulsion is formed at a T-junction of two channels. At the T-junction, the phase to be dispersed is pressed laterally into the continuous phase flowing in a straight line, wherein the emulsion is formed by a regular shear process at the T-junction. The shear technique has disadvantages since the monodispersity of the droplets produced and the possibility of producing emulsions containing a small volume of the continuous phase are limited.
In fluidic microsystems, it is not only the production of dispersions that is of interest, but also the targeted fusion of dispersion droplets in order for example to trigger chemical reactions of reaction partners in adjacent droplets. It is known to fuse dispersion droplets under the effect of an electric field (so-called electrocoalescence). By way of example, electrocoalescence using electrodes in a fluidic microsystem is described by J. and G. Kralj et al. in “Lab Chip”, vol. 5, 2005, page 531, and in WO 2006/027757. The electrodes are arranged a certain distance apart in the longitudinal direction of a channel of the microsystem. When dispersed droplets are located in the gap between the electrodes, the droplets can be fused by applying a fusion voltage to the electrodes. The conventional techniques have a limited use due to the following disadvantages. Firstly, relatively high voltages, sometimes in the kV range, are required for fusion of the droplets. This is associated with problems regarding control of the electrodes and with a disadvantageous influencing of the dispersion by the high electric field. If, for example, sensitive macromolecules such as e.g. biological macromolecules in adjacent droplets are to be made to react, the macromolecules may be damaged in the high-voltage field. Another disadvantage is the limited selectivity of the droplet fusion, which typically involves an unspecified number of droplets in the gap between the electrodes.
The objective of the invention is to provide an improved method for forming an emulsion in a fluidic microsystem, by means of which the disadvantages of the conventional techniques are overcome and which is particularly suitable, with a high degree of monodispersity and/or an increased variability, for setting at least one of the parameters consisting of droplet size, droplet composition, volume ratio of the continuous and dispersed phases and spatial arrangement of the droplets of the dispersed phase. Furthermore, the method is intended to be suitable for use in a fluidic microsystem, in particular during continuous operation of the microsystem (“on-line”). The objective of the invention is also to provide an improved fluidic microsystem for forming an emulsion, by means of which the disadvantages of the conventional techniques are overcome and which is suitable for carrying out the abovementioned method. According to further aspects, the objective of the invention is to provide improved methods and devices for processing emulsions, in particular for fusing dispersed droplets using electric fields, by means of which the disadvantages of the conventional methods can be overcome.
These objectives are achieved by methods and devices of the invention.